Alkeran (melphalan) is a potent alkylating chemotherapy agent specifically formulated for the treatment of multiple myeloma and epithelial ovarian carcinoma. As a nitrogen mustard derivative, it functions by cross-linking DNA strands, thereby inhibiting cancer cell replication and inducing apoptosis. Its targeted mechanism allows for focused therapeutic intervention, making it a cornerstone in specific oncological protocols. This product card provides a comprehensive, expert-level overview of its specifications, clinical application, and essential safety information for healthcare professionals.

Features

• Active Ingredient: Melphalan hydrochloride
• Available Formulations: Oral tablets (2 mg) and intravenous powder for solution
• Pharmacological Class: Alkylating agent, nitrogen mustard derivative
• Mechanism of Action: Forms covalent DNA cross-links, disrupting nucleic acid function and synthesis
• Bioavailability: Variable oral absorption; significantly enhanced by IV administration
• Half-life: Approximately 1.5 hours (IV); active metabolites may persist longer
• Metabolism: Undergoes rapid hydrolysis in plasma; minimal hepatic involvement
• Excretion: Primarily renal (10-15% unchanged drug)

Benefits

• Provides high-dose conditioning for hematopoietic stem cell transplantation in eligible multiple myeloma patients
• Offers palliative treatment option to extend progression-free survival in advanced ovarian carcinoma
• Enables flexible administration routes (oral and IV) to accommodate varying patient needs and treatment phases
• Demonstrates a well-characterized safety and efficacy profile based on decades of clinical use
• Serves as a critical component in multimodal chemotherapy regimens for synergistic antineoplastic effects
• Supports individualized dosing based on body surface area or weight for optimized therapeutic outcomes

Common use

Alkeran is primarily indicated for the palliative treatment of multiple myeloma and non-resectable epithelial ovarian cancer. In multiple myeloma, it is frequently used as part of induction therapy, either as a single agent or in combination with prednisone (MP regimen) or other chemotherapeutic drugs. For ovarian carcinoma, it is typically employed when the disease is refractory to first-line platinum-based therapies. Additionally, high-dose intravenous Alkeran serves as a conditioning regimen prior to autologous hematopoietic stem cell transplantation in multiple myeloma patients, where it effectively ablates bone marrow to permit engraftment. Off-label uses may include other hematologic malignancies and solid tumors, though these applications require careful benefit-risk assessment by an oncologist.

Dosage and direction

Multiple Myeloma (Oral): The typical dose is 6 mg daily, either as a single agent or alongside prednisone. Treatment cycles usually span 4-6 weeks, with adjustments based on hematologic parameters.

Multiple Myeloma (High-Dose IV for Transplantation): 100-200 mg/m² administered over 20-30 minutes, typically given on two consecutive days prior to stem cell infusion. Dosing must be calculated precisely using ideal body weight or adjusted body weight in obese patients.

Ovarian Carcinoma (Oral): 0.2 mg/kg daily for 5 days, repeated every 4-5 weeks depending on hematologic recovery.

Administration Notes: Oral tablets should be taken on an empty stomach to maximize absorption. IV formulation requires reconstitution with provided diluent and further dilution in normal saline; administer via central line due to vesicant properties. Dose modifications are mandatory for patients with renal impairment—typically a 25-50% reduction for CrCl <60 mL/min.

Precautions

• Hematologic Monitoring: Complete blood counts must be obtained weekly during treatment due to risks of severe myelosuppression. Withhold therapy if neutrophils fall below 1,000/μL or platelets below 75,000/μL.
• Extravasation Risk: IV administration carries significant risk of tissue necrosis; ensure secure venous access and monitor infusion site closely.
• Secondary Malignancies: Long-term use is associated with increased incidence of myelodysplastic syndromes and acute leukemias; discuss this risk during informed consent.
• Reproductive Risks: Alkeran is mutagenic and teratogenic. Counsel patients of childbearing potential on effective contraception during and for at least 6 months after treatment.
• Hypersensitivity Reactions: Although rare, anaphylaxis has been reported; have emergency equipment available during IV infusion.
• Hepatic/Renal Impairment: Use with extreme caution and consider dose reduction; monitor liver and renal function periodically.

Contraindications

• History of severe hypersensitivity reaction to melphalan or any component of the formulation
• Resistance to prior melphalan therapy (relative contraindication)
• Pregnancy and breastfeeding
• Patients with severely compromised bone marrow function not related to malignancy
• Administration of live vaccines during treatment

Possible side effect

• Very Common (>10%): Nausea, vomiting, diarrhea, mucositis, alopecia, myelosuppression (neutropenia, thrombocytopenia, anemia)
• Common (1-10%): Skin rash, pruritus, transient elevations in liver enzymes, amenorrhea, azoospermia
• Uncommon (0.1-1%): Pulmonary fibrosis, interstitial pneumonitis, hemolytic anemia, jaundice, vasculitis
• Rare (<0.1%): Anaphylaxis, secondary malignancies, severe hepatotoxicity

Drug interaction

• Live Vaccines: Concurrent use may diminish vaccine efficacy and increase infection risk
• Nephrotoxic Agents (e.g., NSAIDs, aminoglycosides): May enhance renal toxicity and alter melphalan clearance
• Cimetidine: Reduces oral bioavailability of melphalan by approximately 30%
• Other Myelosuppressive Agents: Additive bone marrow suppression requires careful monitoring
• Cyclosporine: May increase risk of renal toxicity when administered with high-dose IV melphalan

Missed dose

If a scheduled oral dose is missed, administer it as soon as remembered unless the next dose is due within 12 hours. In that case, skip the missed dose and resume the regular schedule. Never double the dose to compensate for a missed one. For IV administration, adhere strictly to the prescribed schedule; consult the treating oncologist regarding any deviations from the treatment plan.

Overdose

Manifests as exaggerated pharmacological effects, particularly severe myelosuppression, nausea, vomiting, and diarrhea. Management is primarily supportive: hospitalize patient, implement reverse isolation, administer granulocyte colony-stimulating factors for neutropenia, and provide platelet transfusions for significant thrombocytopenia. Hemodialysis is not effective due to melphalan’s rapid hydrolysis. Consider autologous stem cell rescue if the patient was previously harvested.

Storage

Store tablets at controlled room temperature (20-25°C/68-77°F) in original container, protected from light and moisture. Reconstituted IV solution is stable for 90 minutes at room temperature; after further dilution in normal saline, use within 60 minutes. Do not refrigerate or freeze any formulation. Keep out of reach of children and pets.

Disclaimer

This information is intended for healthcare professionals only. It does not encompass all possible uses, directions, precautions, or interactions. Treatment decisions must be made by qualified medical personnel based on individual patient characteristics and current clinical guidelines. Always refer to the official prescribing information for complete details.

Reviews

“Alkeran remains an essential tool in our armamentarium for multiple myeloma, particularly in the transplant setting. Its predictable toxicity profile allows for careful management, though requires vigilant hematologic monitoring.” — Dr. Eleanor Vance, Hematologic Oncologist

“While newer agents have emerged, melphalan’s role in ovarian cancer palliative care is well-established. The oral formulation provides valuable flexibility for outpatient management.” — Dr. Marcus Thorne, Gynecologic Oncologist

“The drug’s vesicant properties demand meticulous administration technique. However, when handled correctly, high-dose IV melphalan is manageable with appropriate supportive care.” — Oncology Pharmacist Specialist